Biomedical subjects

J M Ledingham

Publications and source records attributed to J M Ledingham.

At least 55 records · Page 3Linked to original sources

PubMed1981

The action of propranolol on factors concerned with the delivery of oxygen to the tissues.

1 In a previous study in conscious rats, orally administered propranolol acutely lowered cardiac output by 30.5% and oxygen uptake by 12.2%, while oxygen extraction rose by 31.5%. The present study is concerned with the way in which the rat meets its oxygen requirements against such a fall in perfusion. 2 The effect of known concentrations of propranolol on haemoglobin-oxygen affinity was studied in vitro. The effect of orally administered propranolol (given acutely and chronically) was then determined and this was related to the concentration of the drug in plasma and red cells. Further studies were made on the action of propranolol on the Bohr effect and on arterial oxygen carriage. 3 In vitro, high concentrations of propranolol (1 x 10(-4) M) influenced haemoglobin-oxygen affinity in a biphasic manner and this was associated with changes in haematocrit and red cell and plasma pH. No change occurred in affinity after acute or chronic oral administration of the drug due to insufficient concentration in the blood. No direct action of the Bohr effect was detected. 4 Arterial oxygen content rose acutely due to an increase in haemoglobin concentration. 5 It is concluded that increased oxygen extraction in propranolol-treated rats is not explained by the actions of the drug on haemoglobin-oxygen affinity.

Animals↗

PubMed1981

Effect of captopril on blood pressure, total body sodium and fluid consumption of genetically hypertensive (GH) and normotensive (N) rats.

Captopril was administered in the drinking fluid to normotensive rats and rats of the New Zealand genetically hypertensive (GH) strain. It lowered BP in both strains of rat, particularly in rats deprived of sodium; in these rats BP rose again when the drug was stopped even though there was no access to sodium. Thus captopril appeared to lower blood pressure not by reduction in total exchangeable sodium but by some other mechanism, presumably inhibition of vasoconstriction. Total exchangeable sodium did not change significantly in rats treated with captopril and having access to salt in the drinking fluid, though it fell in rats deprived of sodium. Captopril caused an increase in fluid intake, particularly intake of 0.5% NaCl solution and this may have compensated for any loss of body sodium. It was not clear whether the thirst for water and the desire for salt were due to effects of captopril in the CNS or were secondary to increased excretion of salt and water.

Animals↗

PubMed1980

Effect of inheritance and stress on the diurnal excretion of sodium and potassium in young people with and without a family history of hypertension.

1. The diurnal excretion of sodium and potassium was observed in young people, with and without a genetic predisposition to hypertension, both in the presence and absence of psychological stress. 2. In the absence of stress, the normal day/night sodium excretion ratio was reversed in the children of hypertensive parents. This was significantly less than day/night sodium excretion in children of normotensive parents. A similar finding was observed for day/night potassium excretion. 3. There was a significant negative correlation between systolic blood pressure and day/night sodium excretion in children of hypertensive parents but not in children of normotensive parents. 4. After the mental stress of a University examination day/night sodium reverted to normal in children of hypertensive parents.

Adult↗

PubMed1979

Effect of isometric exercise on the renal excretion of sodium and potassium in mild hypertension.

1. Basal levels of pulse rate, blood pressure and rates of sodium and potassium excretion were observed in eight white male patients with mild hypertension and eight age-, sex- and colour-matched controls during an initial rest period of 90 min and then for 5 h after a 1 h period of isometric exercise involving all four limbs in rotation. The studies were repeated on another day with the subjects resting instead of exercising for 1 h. 2. Changes in systolic pressure after exercise were similar in the hypertensive and control groups, whereas the rise in diastolic pressure was higher and the rise in pulse rate lower after exercise in the hypertensive group compared with the control group. 3. The changes in the rate of salt excretion were significantly different in the two groups, the hypertensive group retaining proportionately more sodium and potassium over several hours.

Adult↗

PubMed1979

Long-term measurement of total exchangable sodium in one- and two-kidney Golblatt rats.

Total exchangeable sodium (Nae) was measured by wholebody counting of 22Na in 1- and 2-kidney Goldblatt rats before, and for 12 weeks after, renal artery clipping. In 1-kidney Goldblatt rats, Nae relative to body weight increased immediately after the clipping procedure and then fell though not to normal levels; from the 10th to the 12th week it again rose rapidly, probably secondary to vascular damage. In 2-kidney Goldblatt rats, Nae relative to body weight increased immediately after the clipping procedure but by the 5th day it was back to normal and remained normal thereafter. Consideration of the values for absolute Nae (i.e. expressed in mmol per rat) casts some doubt on the reality of the sodium 'retention', except in the 1-kidney Goldblatt rats in the later stages of their hypertension. Immediately after surgery temporary loss of weight (presumably mainly affecting fat stores and muscle) probably accounts for much of the rise in Nae relative to body weight.

Animals↗

PubMed1978

Meningitis in Whipple's disease.

Explore the source record for details and available documents.

Humans↗

PubMed1977

The effect of dietary sodium intake on the blood pressure and cardiac output responses to angiotensin II in unanaesthetized rats.

1. Dose-response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2-5% (w/w) or 0-007% (w/w) sodium and administered in various sequences. 2. Dose-response curves were shifted to the left in rats on a high-, compared with a low-, sodium intake. This response was maintained for 7 days on changing from high to low sodium. 3. There was no difference in the relation between the fall of cardiac output and the rise of blood pressure in any of the experimental groups. 4. Dose-response curves for peripheral resistance showed the same directional change as seen for the pressor response in rats on high- and low-sodium diets. Since depression of cardiac output was proportional to the pressure rise, the absolute change in peripheral resistance was greater than the blood pressure response. The proportional changes were similar. 5. It is concluded that alterations in the pressor response to angiotensin caused by changes in sodium loading are attributable to changes in peripheral resistance and not to changes in the cardiac output response to the acute rise in blood pressure.

Angiotensin II↗

PubMed1977

The role of the kidney in hypertension.

The role of the kidney in hypertension is reviewed in terms of sodium and water homeostasis, of the secretion of renin inappropriate to the state of sodium and water balance and of other renal humoral factors which might be implicated in the hypertensive process. Fundamental to the long-term maintenance of hypertension is an alteration in the relationship between renal perfusion pressure and the excretion of sodium and water. This alteration may be brought about as a result of renal structural damage, sympathetically mediated renal vasoconstriction or the action of renal or extrarenal hormones which modulate sodium and water excretion. When renin is secreted in excess of the prevailing level of sodium and water balance, the generated angiotensin contributes to the hypertension directly through peripheral and renal vasoconstriction. The level of blood pressure in two hypertensive patients with chronic renal failure was found to be highly correlated with the level of plasma renin activity as this was lowered by the administration of a beta-blocking drug. In rats deprived of sodium, renal artery constriction and contralateral nephrectomy was followed by hypertension without any elevation of plasma angiotensin and with a minimal expansion of plasma volume unaccompanied by expansion of extracellular fluid volume. The possible role of this small volume change and of other possible factors in producing hypertension is discussed. Studies in the nephrectomised rat confirmed eariler reports that renal medullayr auto-explants inhibited renoprival hypertension, but neither the identity nor mode of action of the medullary hypotensive factor were further clarified.

Angiotensin II↗

PubMed1976

The influence of sodium intake on the pressor response to angiotensin II in the unanaesthetized rat.

1. Dose-response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2-5% (w/w) or 0-007% (w/w) sodium; the different diets were administered in various sequences. 2. In comparison with those from rats receiving a low sodium diet, the dose-response curves were displaced to the left on the high sodium diet, indicating a greater response to angiotensin, and this displacement persisted for a period of approximately 7 days after the diet was changed from high to low sodium. The dose-response curve subsequently shifted to the right when the low sodium diet was maintained for longer. 3. There was a negative correlation between the slope of the dose-response curve and the basal blood pressure in all groups; the correlation was significant in three out of the five different treatment groups. 4. Basal blood pressures were significantly raised in rats on the high sodium diet for 7 days. 5. A number of possible mechanisms have been considered to explain both the parallel shift of the dose-response curve and alteration in its slope. It is concluded that the observed findings are compatible with an action of sodium-loading on the sensitivity of the smooth muscle cell to angiotensin, on the resting of the renin-angiotensin system, on the rate of inactivation of angiotensin and on a change in initial length of the muscle fibre.

Angiotensin II↗

PubMed1975

Experimental renal hypertension.

The study of hypertension resulting from procedures devised to modify renal function in diverse ways has been pursued intensively in the past forty years and has contributed greatly to the understanding of hypertensive processes in man. Such procedures have included partial or complete removal of renal tissue, interference with the renal circulation and the administration of sodium and hormones promoting the tubular reabsorption of sodium. From all these studies, certain basic conclusions can be drawn. The fundamental mechanism involved in all forms of renal hypertension appears to be an alternation in the relationship between renal perfusion pressure and sodium and water excretion. The probable way in which this fundamental mechanism operates is outlined. The kidney itself is susceptible to the effects of hypertension and changes take place within it which then contribute a renal element to the hypertension whatever its primary cause.

Acute Disease↗

PubMed1974